Medical materials are used, for example, for implants, microsensors and other products which are placed in the human or animal body. In this context the medical materials directly come into contact with the tissue and the cells of the body. In their natural environment cells are surrounded by an extracellular matrix which is important for the survival of the cells, since it decisively influences their adhesion, proliferation, migration, differentiation and function. The main components of the extracellular matrix are hydrogels and polymer fibres which are not water-soluble, these serving as a mechanical scaffold. Basal membranes and ultrathin separating layers between tissues are also present. These structures are matched to the different biological requirements of various organs and tissues. In order to promote a good interaction between the cells and the medical materials, attempts are made to adapt the structure and composition of the materials to the natural environment of the cells.
DE 19751031 A1 describes highly pure collagen sponge products having an open pore structure which shall enable growth of the cells into the sponge. A freezing process with which a homogeneous and targeted distribution of the collagen fibres in channel-like guiding structures is generated by finger-shaped ice crystals growing through a collagen type I dispersion is used for production of the collagen sponges. For this, analogously to the common processes of metalworking, freezing processes have been designed which structure a mixture of substances between two temperature-controllable surfaces which are arranged parallel or concentrically with respect to one another by keeping the temperature gradient between the surfaces constant. The mixture structured in this manner is then freeze-dried by precooling it under overpressure and releasing the pressure suddenly. However, the materials obtained in this way exclusively consist of one single functional component, namely collagen type I, and therefore can reproduce the natural environment of cells to only a limited extent.
Tampieri et al., 2008 describe the combination of three layers of collagen scaffolds of different composition to form an overall structure, each scaffold representing a different bone or cartilage layer. The top layer consists of pure collagen I and serves as a chondral zone replacement. Collagen I mineralized by a precipitation reaction with hydroxylapatite, with a mineral-matrix ratio of 70/30 wt. %, replaces the subchondral bone. However, an intermediate layer mineralized in the same manner, in a mineral-matrix ratio of 40/60 wt. %, differs significantly from the tidemark of native chondral tissue. The hydroxylapatite of the subchondral zone here is partially doped by magnesium. The individual collagen scaffolds were each crosslinked separately by 1,4-butanediol diglycidyl ether (BDDGE) and bonded to one another using a “weaving process”. The overall structure was then freeze-dried. Cell experiments showed, however, that the structure produced in this way allows only a limited population by cells. Thus, only a low cell migration into the inside of the chondral replacement zone with a non-uniform distribution was to be observed, whereas the region in the centre of the scaffold remained substantially acellular. A complete integration of the material after implantation is therefore not possible.
EP 1858562 B1 describes a porous, three-layered, osteochondral scaffold. This comprises a zone covered with a smooth surface, which is made to the extent of 100% of collagen I of equine origin and shall correspond to chondral tissue. The region of the subchondral and osteal zone is represented by composites of collagen type I and nanostructured, magnesium-enriched hydroxylapatites. The individually produced zones, however, are joined together only subsequently by a compression operation, as a result of which a delamination may occur during rehydration of the freeze-dried matrices. Moreover, histological results of animal studies show that only fibrous chondral tissue but no native articular chondral tissue is formed in the chondral zone. Such fibrous chondral tissue is formed above all during the natural but rare and incomplete self-healing processes of the cartilage. In addition to the collagen type II mainly occurring in healthy articular cartilage, it also comprises atypical collagen type I and differs decisively in structure and functionality from native chondral tissue. The adverse formation of fibrous chondral tissue is possibly to be attributed to the fact that the chondral replacement zone only consists of one individual layer, which has an atypical composition compared with native cartilage and too large porosities with an unnatural alignment.
There is therefore the need for stable materials which have functionally different regions which reproduce the natural environment of cells.